Rhythm Control in Afib Linked to More Hospitalizations

Action Points

The AFFIRM trial previously demonstrated that, in patients with atrial fibrillation, rhythm control does not offer a survival benefit over rate control.

This re-analysis used propensity matching to evaluate the impact of specific rhythm control drugs on a composite endpoint of death and cardiovacsular hospitalization.

Note that the composite outcome was significantly more common in all three of the rhythm control arms (amiodarone, sotalol, class 1c agents). This finding was driven primarily by an increased number of cardiovascular hospitalizations.

Rate control topped rhythm control for reducing cardiac hospitalizations and death in high-risk patients with atrial fibrillation (Afib), a new analysis of a randomized trial showed.

Patients treated with amiodarone, sotalol, or class 1C antiarrhythmics had an increased risk of deaths and cardiovascular hospitalization compared with patients managed with rate-controlling drugs.

The magnitude of the hazard ranged from 18% to 32%, depending on the type of rhythm-control drug used.

The higher hazard with antiarrhythmic therapy owed largely to increased rates of cardiovascular hospitalization, investigators reported in the Nov. 1 issue of the Journal of the American College of Cardiology.

"CV hospitalizations in AFFIRM [Atrial Fibrillation Follow-Up Investigation of Rhythm Management] occurred with both treatment strategies, but were more frequent with amiodarone, sotalol, and class 1C agents," Sanjeev Saksena, MD, of Robert Wood Johnson Medical School in Warren, N.J., and co-authors wrote in conclusion.

"The severity of this risk varied with individual antiarrhythmic drug, patient characteristics, and time-dependent changes in clinical status, but was largely unrelated to the rhythm treatment algorithm. Death, intensive care unit hospital stay, and non-CV death were more frequent with amiodarone."

Afib is associated with increased mortality, stroke risk, and length of hospital stay, the latter of which substantially increases resource utilization. The relationship of hospitalization to specific therapies for Afib has not been evaluated, according to the authors' background discussion.

The AFFIRM trial evaluated the strategies of rate and rhythm control in high-risk Afib patients. The primary outcome was a trend toward increased mortality in those randomized to rhythm control.

The drugs employed in the rhythm-control arm have been suggested as the source of the unfavorable mortality trend, but no data had been reported to support or refute the suggestion, the authors continued.

To evaluate the potential impact of specific rhythm-control therapies on outcome in AFFIRM, Saksena and colleagues performed a propensity-matching analysis to compare the rate-control strategy with each rhythm-control cohort, as defined by the individual antiarrhythmic drugs (which were not randomly assigned in AFFIRM).

The primary outcome was the composite endpoints of mortality or first cardiovascular hospitalization, as well as the individual endpoints.

Secondary outcomes related to severity of hospital stay, as characterized by stay in an intensive care unit, cardiovascular procedures and interventions, and emergency department visits.

The analysis included 729 patients initially randomized to amiodarone, 606 to sotalol, and 268 to class 1C antiarrhythmic drugs.

Patients assigned to all three classes of rhythm-control therapy had inferior outcomes compared with patients randomized to rate control:

Amiodarone, HR 1.18, P=0.02

Sotalol, HR 1.32, P<0.001

Class 1C antiarrhythmics, HR 1.22, P=0.10

Analysis of the individual components of the composite endpoint showed no significant increase in mortality by specific rhythm-control treatment assignment, but patients in the amiodarone group had a trend toward higher mortality (HR 1.20, P=0.15).

All three rhythm-control groups had higher rates of cardiovascular hospitalization compared with rate control:

Amiodarone, HR 1.20, P=0.05

Sotalol, HR 1.36, P<0.001

Class 1C antiarrhythmics, 1.24, P=0.09

The authors found that 91% of patients in the amiodarone group were still on initial therapy at the time of first hospitalization, as were 88% of sotalol patients, and 78% of patients randomized to class 1C antiarrhythmics.

Patients in the three rhythm-control strategies had higher rates of hospitalization with cardioversion lasting fewer than three days as compared with their matched rate-control cohorts (11% to 12% versus 3% to 4%).

Rates of hospitalization with cardioversion but no other procedures or interventions were 5% to 6.1% among the rhythm-control groups compared with 1.6% to 1.9% for the rate-control groups.

Although the study showed an increased rate of cardiovascular hospitalization in the rhythm-control groups, the analysis did not explain why, as reasons for hospital stay were not reported in AFFIRM, Steven Markowitz, MD, of Cornell University Medical Center in New York, wrote in an accompanying editorial.

"The higher rate of cardiovascular hospitalization in the rhythm-control subgroups could not be explained by hospital admissions to change antiarrhythmic drugs or perform cardioversion, which comprised a small percentage of the hospital stays," Markowitz continued. "Most hospital stays were long (more than three days), and many involved intensive care unit stays, suggesting severe illness.

"One might speculate that antiarrhythmic drug-treated patients were hospitalized more often because of worsening heart failure," he said.

The findings of the analysis notwithstanding, "it is premature to regard rhythm-control as a futile endeavor," Markowitz added. "As has been acknowledged elsewhere, the results from rate- versus rhythm-control trials cannot necessarily be applied to younger patients, those with fewer comorbidities, or those who poorly tolerate AF despite rate-control attempts."

"Even among those at higher risk, sinus rhythm might be preferable. A subanalysis of the AFFIRM trial indicated that maintenance of sinus rhythm was independently associated with better survival, potentially counter-balanced by the worsened survival associated with [antiarrhythmic drug] exposure."

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